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ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin

Nature Neurosciencevolume 9pages5866 (2006) | Download Citation



Networks in the CNS consist of neural modules that are connected in a repetitive array. Whereas individual modules contain guidance information along which axons track within the unit, these guidance cues hinder axon extension across module boundaries. We investigated how axons solve this 'boundary problem' by analyzing the longitudinal connections of neuromeres in Drosophila melanogaster. The initial trajectory of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled. The Netrin cue on the commissure of the next segment can act as a barrier to longitudinal axons, inhibiting their extension and misguiding them contralaterally along the commissure. We show that, before reaching the segmental boundary, the longitudinal axons' responsiveness to Netrin presented on the commissure is suppressed by Roundabout (ROBO), through counteracting Gq signaling. The absence of suppression causes the robo phenotype: longitudinal axons project toward the midline, as if running around a roundabout (rotary).

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We thank C.S. Goodman, A. Hidalgo, P. Kolodziej, M. Seeger, G. Technau, A. Ratnaparkhi and the Bloomington Stock Center for fly strains; P. Kolodziej, M. Seeger and the DSHB for fly DNA clones and antibodies; M. Matsushita and S. Li for the GFP-IP3 sponge cDNA; K. Takei for helpful advice on the IP3 experiment; T. Katsuki, T. Nagasaka and all the members of the Hiromi laboratory for helpful discussions; Y. Iketani, M. Aono and C. Asaka for technical assistance; and E. Giniger and S. Butler for helpful advice on the manuscript. This work was funded by the Precursory Research for Embryonic Science and Technology (M.H.) and the Core Research for Evolutional Science and Technology (Y.H.) programs of the Japan Science and Technology Agency. Funding was also provided by the Japan Society for the Promotion of Science (M.H.) and the Ministry of Education, Science, Sports and Culture of Japan (Y.H.).

Author information


  1. Department of Developmental Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan

    • Masaki Hiramoto
    •  & Yasushi Hiromi
  2. Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Honcho, Kawaguchi-shi, Saitama, 332-0012, Japan

    • Masaki Hiramoto
  3. Japan Society for the Promotion of Science, SOKENDAI, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan

    • Masaki Hiramoto
  4. Department of Genetics, SOKENDAI, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan

    • Yasushi Hiromi
  5. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Honcho, Kawaguchi-shi, Saitama, 332-0012, Japan

    • Yasushi Hiromi


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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Masaki Hiramoto or Yasushi Hiromi.

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  1. Supplementary Fig. 1

    Sequential patterning of commissural and longitudinal axons. (PDF 6033 kb)

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